Effect of MTHFR, TGFβ1, and TNFB polymorphisms on osteoporosis in rheumatoid arthritis patients

Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

doi:10.1016/j.gene.2015.05.037

Cited by 10 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, TGF-β has been reported to affect chondrocytes and inhibit the generation of collagen type II, while in osteoblasts it induced COL1 production, thus reducing the cartilage damage period during bone repair ( 15 ). TGF-β has also been reported to promote matrix differentiation ( 31 ). In the present study, overexpression of miR-214-5p suppressed TGF-β protein expression in HBMSCs.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β and various cytokines have been previously reported to regulate the activity of Runx2 ( 32 ), which is an essential protein for the skeleton growth process. In vitro experiments demonstrated that TGF-β promoted the proliferation and differentiation of ectomesenchymal cells periosteum, promoted the proliferation of osteogenesis (cartilage) cells and stimulated osteogenesis-associated genes, including increases in Runx2 mRNA expression and the synthesis of osteonectin, osteopontin and COL1 ( 31 ). Furthermore, it was demonstrated to inhibit the generation of osteoclasts and the activity of mature osteoclasts, thus inhibiting bone resorption and reducing concomitant markers ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

Qiu

Huang

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Postmenopausal osteoporosis (OPM) is a common type of osteoporosis in females. It is a systemic, chronic bone disease that presents as microstructure degradation of osseous tissue, decreased bone mineral density and increased osteopsathyrosis caused by hypoovarianism and reduced estrogen levels in the body following menopause. In the present study, the role of microRNA (miR)-214-5p in the regulation of the expression of bone marrow stem cells (BMSCs) was investigated, and its molecular mechanism of osteogenic induction in vitro was assessed. When dexamethasone-induced adipogenic differentiation was performed, miR-214-5p expression was increased compared with the control group, as determined by RT-qPCR. Furthermore, oil red O staining, RT-qPCR and western blot analysis demonstrated that overexpression of miR-214-5p promoted adipogenic differentiation, inhibited alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OC) and collagen α-1 (I) chain (COL1A1) mRNA expression, and suppressed transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and collagen type IV α1 chain (COL4A1) protein expression in BMSCs. Additionally, downregulation of miR-214-5p increased the ALP, Runx2, OC and COL1 mRNA expression and increased TGF-β, Smad2 and COL4A1 protein expression in BMSCs. Furthermore, a TGF-β inhibitor was employed to inhibit TGF-β expression in BMSCs following miR-214-5p downregulation, which led to reduced Smad2, TGF-β and COL4A1 protein expression, and ALP, Runx2, OC and COL1 mRNA expression was also reduced, compared with the miR-214-5p downregulation only group. It was demonstrated that miR-214-5p may weaken osteogenic differentiation of BMSCs through regulating COL4A1. In conclusion, the results of the present study indicated that miR-214-5p may promote the adipogenic differentiation of BMSCs through regulation of the TGF-β/Smad2/COL4A1 signaling pathway, and potentially may be used to develop a novel drug for postmenopausal osteoporosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

Qiu

Huang

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…RA pathogenesis is an active area of research including several genes. MTHFR , TGFβ1 , TNFB , and VDR genes have generated great interest in RA pathogenesis [ 1 , 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis

et al. 2015

Self Cite

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR—C677T and A1298C, TGFβ1 T869C, TNFB A252G, and VDR—ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co-dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGFβ1 and MTHFR A1298C were associated with RA using the dominant and the co-dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D′ value between BsmI and FokI (D′ = 0.91), but the r2 value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP.

show abstract

“…Previous studies have investigated associations between RA clinical activity and treatment response and the deoxyribonucleic acid (DNA) variants of genes associated with folic acid metabolism such as MTRR , RFC1 , and MTHFR (Berkun et al , 2004 ; Hughes et al , 2006 ; Wessels et al , 2006 ; Rubini et al , 2008 ; Inanir et al , 2013 ; Salazar et al , 2014 ; Saad et al , 2015a , 2015b , 2016 ; Muralidharan et al , 2016 ; Remuzgo-Martínez et al , 2016 ). MTRR gene is located on chromosome 5p15.3 and encodes for the enzyme methionine synthase reductase, involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state (Jacques, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

González-Mercado

Rivas

Gallegos‐Arreola³

et al. 2017

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

Aim: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX).Materials and Methods: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction.Results: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations.Conclusion: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA.

show abstract

Effect of MTHFR, TGFβ1, and TNFB polymorphisms on osteoporosis in rheumatoid arthritis patients

Cited by 10 publications

References 27 publications

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis

MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

Contact Info

Product

Resources

About